NSAIDs in Rheumatology: Benefits, Risks and How to Use Them Safely
Non-steroidal anti-inflammatory drugs—usually shortened to NSAIDs—are among the most frequently used medicines for joint and musculoskeletal pain.
Some, such as ibuprofen, can be bought without a prescription. Others, including naproxen, diclofenac, celecoxib and etoricoxib, are commonly prescribed. This familiarity can make NSAIDs seem relatively simple, but they are powerful medicines with genuine benefits and important risks.
For the right patient, an NSAID can reduce pain, stiffness and inflammation and make movement considerably easier. For someone with kidney disease, a history of stomach ulcers, heart failure or particular medication combinations, the same treatment may cause significant harm.
The question is therefore not whether NSAIDs are “good” or “bad.” It is whether a particular NSAID is appropriate for a particular person, at a suitable dose, for an appropriate length of time.
What are NSAIDs?
NSAIDs reduce the production of prostaglandins—chemical messengers involved in pain, inflammation, fever and several normal protective functions within the body.
They do this by inhibiting enzymes called cyclo-oxygenase, usually abbreviated to COX. Traditional NSAIDs affect COX-1 and COX-2 to varying degrees. Medicines such as celecoxib and etoricoxib are more selective for COX-2 and are often called COX-2 inhibitors or coxibs.
Reducing prostaglandin activity can relieve pain and inflammation. However, prostaglandins also help protect the stomach lining, support blood flow through the kidneys and contribute to normal vascular function. This explains why the same mechanism that makes NSAIDs effective can also produce stomach, kidney, blood-pressure and cardiovascular problems.
What symptoms can NSAIDs help?
NSAIDs can be useful across several different areas of rheumatology.
They may reduce pain and stiffness in inflammatory arthritis, including rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis. They can treat acute crystal inflammation during a gout or pseudogout flare. They may help osteoarthritis, back pain and selected tendon or bursal problems.
Their role differs between these conditions.
In osteoarthritis or a self-limiting soft-tissue problem, an NSAID may be used mainly to make movement and rehabilitation easier. In an acute gout flare, it may directly suppress the intense inflammatory response around urate crystals. In rheumatoid arthritis, it may improve symptoms while disease-modifying treatment begins to work.
A good response to an NSAID does not prove that a condition is autoimmune or inflammatory. Mechanical pain can also respond. Conversely, a poor response does not exclude inflammatory disease.
NSAIDs relieve symptoms but are not usually disease-modifying
One of the most important distinctions is between controlling symptoms and changing the underlying disease.
NSAIDs may improve pain, stiffness and swelling, but they do not usually prevent joint damage in rheumatoid or psoriatic arthritis. They do not treat lupus-related organ disease, vasculitis or polymyalgia rheumatica, and they cannot replace a DMARD, biologic treatment or steroid when one of those is clinically required.
In axial spondyloarthritis, NSAIDs have a particularly important role as an initial treatment for pain and stiffness. However, persistent active disease may require further assessment and targeted treatment.
Someone who feels better after taking an NSAID may understandably assume that the underlying problem has been treated. In inflammatory arthritis, symptom improvement can be valuable, but the disease itself may still require a longer-term plan.
This distinction is related to the broader question explored in What Do Rheumatologists Mean by Inflammation?.
Are all NSAIDs the same?
NSAIDs belong to the same broad family, but they are not interchangeable.
They differ in duration of action, dose, gastrointestinal risk, cardiovascular profile, kidney effects and suitability for particular patients. A person who develops indigestion with one may tolerate another, but switching drugs does not remove the underlying class risks.
Ibuprofen is short-acting and widely available without prescription. Naproxen lasts longer and is commonly used for inflammatory musculoskeletal pain. Diclofenac can be effective but requires particular cardiovascular consideration. Celecoxib and etoricoxib are more selective for COX-2 and may produce fewer upper-gastrointestinal problems in some patients, although they still have cardiovascular, kidney and other risks.
There is no universally safest NSAID. The most appropriate choice depends on why it is being used and the patient’s medical history.
Taking two different NSAIDs together is generally not appropriate. Combining ibuprofen with naproxen, diclofenac or another oral NSAID is more likely to increase toxicity than to provide worthwhile additional benefit.
NSAIDs and axial spondyloarthritis
NSAIDs have a particularly important role in axial spondyloarthritis, where they are recommended as the first-line drug treatment for inflammatory back pain and stiffness. Some patients respond strikingly well.
Selective COX-2 inhibitors, including celecoxib and etoricoxib, can be effective options, particularly when gastrointestinal tolerability is a concern. However, they are not consistently more effective than traditional NSAIDs such as naproxen or diclofenac. Response varies between individuals, so it is often reasonable to try a different NSAID if the first does not provide adequate relief.
The choice should not be based on effectiveness alone. Gastrointestinal, cardiovascular, kidney and blood-pressure risks still need to be considered, and COX-2 selectivity does not make a medicine risk-free. NSAIDs should also not be continued solely in the hope of preventing spinal damage: current evidence is insufficient to recommend them for this purpose when they are not needed for symptom control.
Topical NSAIDs
NSAIDs can also be applied to the skin as gels, creams, sprays or patches.
Topical treatment delivers a lower total amount of medicine to the bloodstream than an oral NSAID and may therefore reduce—but not completely eliminate—systemic risk. It can be particularly useful when pain is localised to a superficial joint or soft-tissue structure, such as a knee, hand or tendon.
Topical preparations are less likely to help deep structures such as the hip or spine. They may also cause local skin irritation, and patients should follow instructions about dose, application and handwashing.
For knee osteoarthritis, NICE recommends offering a topical NSAID before moving to an oral preparation. It may also be considered for osteoarthritis affecting other joints. NICE osteoarthritis guidance.
Someone using a topical NSAID should still mention it when discussing medication. Using topical and oral preparations together may increase overall exposure.
The stomach and gastrointestinal bleeding
Stomach symptoms are among the best-known NSAID side effects.
NSAIDs can cause indigestion, gastritis, ulcers and gastrointestinal bleeding. Some people develop warning symptoms such as upper-abdominal pain or persistent heartburn. Others may develop an ulcer or bleeding without much preceding discomfort.
Risk is higher in people with a previous ulcer or gastrointestinal bleed, older adults and those taking an NSAID at a higher dose or for longer periods. It also rises when NSAIDs are combined with corticosteroids, anticoagulants, antiplatelet medicines or certain antidepressants.
Taking an NSAID with or after food may reduce dyspepsia, but it does not reliably prevent an ulcer or gastrointestinal bleed.
A proton-pump inhibitor—or PPI—such as omeprazole or lansoprazole is often prescribed for stomach protection, particularly when oral NSAIDs are used regularly or when gastrointestinal risk factors are present. A PPI reduces upper-gastrointestinal risk but does not protect the kidneys, blood pressure or cardiovascular system.
Black, tarry stools, vomiting blood or material resembling coffee grounds, faintness or unexplained severe abdominal pain require urgent medical assessment.
Kidney function and dehydration
NSAIDs can reduce blood flow through the kidneys. Most healthy people taking a short course will not develop a serious kidney problem, but risk changes considerably with age, dehydration, existing kidney disease and other medication.
Particular care is required during vomiting, diarrhoea, fever or poor fluid intake. A dose that was previously tolerated may become unsafe when someone is dehydrated or acutely unwell.
The combination of an NSAID with an ACE inhibitor or angiotensin-receptor blocker and a diuretic is sometimes described as the “triple whammy.” These medicines are commonly used for high blood pressure, heart failure and kidney disease. Together, particularly during dehydration, they can substantially increase the risk of acute kidney injury.
This does not mean that every person taking one of these combinations will develop kidney failure. It means that the indication, dose, hydration and kidney function require careful review.
Reduced urine output, new ankle swelling, sudden weight gain or unexplained breathlessness while taking an NSAID should prompt medical advice.
Blood pressure, fluid retention and cardiovascular risk
NSAIDs can raise blood pressure, promote fluid retention and reduce the effectiveness of some antihypertensive medicines. They may worsen heart failure and can increase the risk of cardiovascular events in susceptible people.
The size of this risk varies according to the medicine, dose, duration and patient. Short-term, low-dose treatment in a younger person without cardiovascular disease is different from continuous high-dose treatment in someone with previous heart attack, stroke, uncontrolled hypertension or heart failure.
Diclofenac and COX-2 inhibitors require particular caution in people with established cardiovascular disease. Naproxen and low-dose ibuprofen are generally considered to have more favourable thrombotic profiles, but neither is free of cardiovascular, gastrointestinal or kidney risk.
For all NSAIDs, the underlying principle is to use the lowest effective dose for the shortest appropriate duration and to review ongoing need periodically.
Further context is available in Rheumatic Disease and Cardiovascular Risk.
NSAIDs and asthma
Most people with asthma can take NSAIDs, but a minority develop worsening wheeze, nasal symptoms or breathing difficulty after aspirin or another NSAID.
This is more likely in people with a history of nasal polyps, chronic sinus disease or a previous respiratory reaction to aspirin or ibuprofen. It is sometimes called NSAID-exacerbated respiratory disease.
Anyone who has previously experienced wheezing, facial swelling or breathing difficulty after an NSAID should not try another preparation without medical advice.
Sudden breathing difficulty or swelling of the lips, tongue or throat requires emergency treatment.
NSAIDs and methotrexate
Patients taking methotrexate are often concerned when they see warnings about NSAIDs.
NSAIDs can reduce the kidney elimination of methotrexate and may increase the risk of kidney or methotrexate toxicity. The risk is greater with high-dose methotrexate, impaired kidney function and additional factors affecting drug clearance.
However, low-dose methotrexate and prescribed NSAIDs are frequently used together in rheumatology under specialist supervision. This combination is not automatically prohibited.
The important distinction is between a treatment plan that has been considered and monitored, and adding over-the-counter ibuprofen or another NSAID without the prescriber knowing.
Patients taking methotrexate should discuss non-prescription NSAIDs with their doctor or pharmacist. Mouth ulcers, severe sore throat, unusual bruising or bleeding can be signs of methotrexate toxicity and should be reported.
Other important medicine interactions
NSAIDs may interact with anticoagulants such as warfarin, apixaban, rivaroxaban or edoxaban by increasing bleeding risk. They can also create problems when combined with antiplatelet medicines such as aspirin or clopidogrel.
Corticosteroids may add to gastrointestinal risk. ACE inhibitors, angiotensin-receptor blockers and diuretics may increase kidney concerns. NSAIDs can raise lithium levels and may interact with several other prescribed medicines.
Cold and flu remedies sometimes contain ibuprofen or another NSAID. Patients may therefore take duplicate treatment without realising it.
A medication review should include prescriptions, over-the-counter products, topical preparations and supplements rather than only the medicines appearing on a repeat-prescription list.
Stomach protection does not make an NSAID risk-free
PPIs are valuable medicines and may substantially reduce the risk of ulcers and upper-gastrointestinal bleeding. However, patients sometimes assume that taking omeprazole means an NSAID can then be used without limitation.
It cannot.
Stomach protection does not prevent kidney injury, fluid retention, raised blood pressure, heart failure or cardiovascular events. It also does not remove every gastrointestinal risk.
The decision to continue an NSAID should still be based on whether it is providing a meaningful benefit and whether the dose and duration remain appropriate.
Pregnancy, fertility and breastfeeding
NSAID use during pregnancy requires particular care.
Current MHRA advice is to avoid systemic NSAIDs from week 20 of pregnancy unless they are clinically necessary and recommended by a healthcare professional. Prolonged exposure from this stage can affect fetal kidney function and amniotic-fluid volume and may constrict an important fetal blood vessel.
Systemic NSAIDs are contraindicated after 28 weeks because of risks including premature closure of the ductus arteriosus, fetal renal dysfunction, prolonged maternal bleeding and effects on labour.
Earlier pregnancy exposure also needs individual consideration. NSAIDs may temporarily interfere with ovulation in some women, which can be relevant when trying to conceive.
Advice during breastfeeding depends on the specific medicine, dose and the health and age of the baby. Pregnant or breastfeeding patients should not assume that an over-the-counter product is automatically safe.
Older adults
Age alone does not make NSAID treatment inappropriate, but older adults are more likely to have factors that increase risk.
Kidney function may be reduced even when someone feels well. High blood pressure, heart failure, anticoagulant use and previous ulcers are more common. Acute illness and dehydration may have greater consequences.
If an NSAID is necessary, the choice and dose should be reviewed carefully. Kidney function, blood pressure and haemoglobin may need monitoring, particularly with regular or prolonged treatment.
Repeatedly issuing an NSAID without checking whether it is still helping is not good long-term prescribing.
Can NSAIDs be used long term?
The phrase “shortest possible duration” does not mean that every NSAID prescription must last only a few days.
Some patients with axial spondyloarthritis or another persistent inflammatory condition gain substantial benefit from longer treatment. Others use an NSAID intermittently during predictable flares. In these situations, ongoing treatment may be reasonable if the benefits are clear and relevant risks are monitored.
Long-term treatment should have a defined purpose. It should be reviewed if symptoms no longer respond, if the dose steadily increases or if new medical problems develop.
Continuing a medicine because it has remained on the repeat prescription for years is different from making an informed decision that its benefits still outweigh its risks.
What monitoring may be needed?
Monitoring depends on the individual and how the NSAID is being used.
A short course in an otherwise healthy adult may require no blood tests. Longer treatment, older age or relevant medical conditions may justify checking kidney function, blood pressure and a full blood count. Liver tests may sometimes be appropriate.
Monitoring should also establish whether the medicine is achieving anything. If pain and function are unchanged, accepting ongoing risk makes little sense.
The same applies when pain is caused by a problem unlikely to respond to an NSAID. Accurate diagnosis remains more valuable than repeatedly trying different anti-inflammatory medicines.
When should NSAIDs be avoided or reviewed carefully?
Particular caution is needed in people with previous gastrointestinal bleeding or active ulcer disease, significant kidney impairment, uncontrolled blood pressure, heart failure, established cardiovascular disease, anticoagulant treatment, previous NSAID allergy or respiratory reaction, and pregnancy.
This does not create one universal list of people who can never receive an NSAID. Some situations represent clear contraindications; others require a different medicine, lower dose, shorter course, gastroprotection or closer monitoring.
The safest decision depends on the indication as well as the risk. A medicine offering little expected benefit should not be accepted simply because its risks can be monitored.
Warning symptoms while taking an NSAID
Urgent assessment is required for vomiting blood, black stools, severe abdominal pain, marked reduction in urine output, rapidly increasing swelling or breathlessness.
Chest pressure, sudden neurological symptoms or possible signs of a blood clot require emergency assessment. So do facial swelling, severe wheeze or difficulty breathing after taking an NSAID.
Less dramatic symptoms—including persistent indigestion, ankle swelling, rising blood pressure or new bruising—should still prompt a medication review rather than simply being tolerated.
A practical approach
NSAIDs are most useful when there is a clear reason for prescribing them and an agreed method of judging whether they are helping.
The patient should know whether the medicine is intended for a short flare, intermittent use or regular treatment. They should know whether stomach protection or blood-test monitoring is required and which over-the-counter products to avoid.
Prescribers should consider the complete medical and medication history rather than selecting an NSAID solely on the basis of pain severity.
The lowest effective dose and shortest appropriate duration remain sensible principles, but safe use is not simply about reducing the number of tablets. It is about choosing the right medicine, for the right problem, in the right patient.
The bottom line
NSAIDs can be extremely effective medicines. They reduce pain, stiffness and inflammation and can make an important difference to mobility and quality of life.
They are not, however, simple painkillers. They may affect the stomach, kidneys, blood pressure, heart and interactions with other medicines. Buying them without a prescription does not make them risk-free.
Good NSAID prescribing balances benefit against individual risk. It distinguishes short-term symptom relief from long-term disease control, avoids unnecessary combinations and reviews whether ongoing treatment remains worthwhile.
Used selectively and monitored appropriately, NSAIDs remain valuable tools in rheumatology. Used automatically or without attention to the wider medical picture, they can cause avoidable harm.
This article provides general information and does not constitute individual medical advice. Patients should seek advice from their doctor or pharmacist before starting or changing an NSAID, particularly if they have other medical conditions, take prescribed medication or are pregnant.